Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer
Key findings
AAV9.45 and AAV9.61 engineered through rational mutagenesis to reduce liver tropism while maintaining cardiac and skeletal muscle transduction. AAV9.45 showed 5-fold reduction in liver uptake. AAV9.61 demonstrated 10-fold improved cardiac:liver ratio. Critical for systemic gene therapy applications.